Myeloma (cont.)

Medical Treatment

Standard first-line (primary) therapy for myeloma involves corticosteroid therapy, with or without chemotherapy. Supportive care is frequently given in conjunction with treatment. However, current investigations may eventually change the approach to first-line treatment of myeloma to nonchemotherapeutic approaches. Sometimes radiation therapy is added forpeople with significant bone damage.

Chemotherapy

Chemotherapy is the use of powerful drugs to kill cancer cells. Chemotherapy is a systemic therapy, meaning that it circulates through the bloodstream and affects almost all parts of the body. Ideally, chemotherapy can find and kill cancer cells throughout the body.

Unfortunately, chemotherapy also affects healthy cells, which accounts for its well-known side effects.

• The side effects of chemotherapy depend partly on the drugs used and the doses.
  
  
• Some people, due to variability in drug metabolism, tolerate chemotherapy better than others.
  
  
• The most common general side effects of chemotherapy include fatigue, increased susceptibility to infections, nausea and vomiting, loss of appetite, hair loss, sores in the mouth and digestive tract, muscle aches, and easy bruising or bleeding.Specific drugs may confer other specific side effects.
  
  
• Medications and other treatments are available to help people tolerate these side effects, which can be severe and, rarely, life-threatening, especially in the elderly.
  
  
• It is important that a patient review the expected outcomes and potential side effects of therapy with their health care provider prior to embarking on their selected course of treatment.

Clinical Trials

New therapies and novel ways to administer known therapies are continually under investigation for the treatment of multiple myeloma.These novel therapies come about as a result of favorable performance in earlier, monitored, national multi-institutional studies.Usually, a clinical trial is offered to patients in order to extend and confirm the earlier results of such studies.In order to receive such new therapies, a patient would have to agree to treatment by enrolling in a clinical trial.

Ideally, the treating hematologist/oncologistwill belong to a clinical trial network that provides up-to-date therapy and instant analysis of ongoing data. Patient enrollment in any clinical trial involvesagreeing to a particular treatmentplan that is exquisitely detailed by the physician and other members of the treatment team. A written protocol is providedto the patient and includes a fully detailed/informed written consent document.

The protocol, and its associated consent form, details the medications, all known side effects, and alternatives to treatment should there be failures in therapy or patient refusal to participate. As noted, the patient is fully apprised of the potential benefits and risks associated with such treatment, and consent is obtained in the presence of the treating physician and very likely other members of the treatment team.

Alternatively, a hematologist-oncologist may refer a patient to another institution to receive investigational treatment or intensive treatment, which may be otherwise unavailable at the current institution,such as stem cell transplantation.

Radiation therapy

Radiation therapy uses high-energy rays to kill cancer cells. It is considered a local therapy, meaning that it should be used to target areas of the body involved by myeloma. A radiation oncologistplans and supervises therapy.

• In myeloma, radiation is used primarily to treat solitary plasma cell tumors, larger tumors, or to prevent a pathologic fracture in a myeloma-compromised bone.
  
  
• In people with extensive disease, radiation may be applied to a larger area to kill off multiple sites of myeloma.
  
  
• Radiation may be used to relieve pain and other symptoms related to a small area of particularly severe bone damage.
  
  
• Total body irradiation (TBI), which involves the entire body,is administered only for people undergoing stem-cell transplantation.
  
  
• Depending on how and where the radiation is administered, it may cause certain side effects such as fatigue, loss of appetite, nausea, diarrhea, and skin problems. Radiation of lymph node areas may result in suppression of the immune system to varying degrees. Irradiation of underlying bone and the marrow within the bone may result in suppression of the blood counts.
  
  
• The schedule for radiation treatments depends on the dose and the treatment goals. Radiation is often administered in short bursts over several days or weeks in order to minimize side effects without losing therapeutic efficiency.

Stem-cell transplantation

Stem-cell transplantation is often used as consolidation therapy after a patient has achieved a complete remission (CR), or after a second CR is achieved in recurrent disease.It is also used in patients who are unable to achieve a remission with first line, or so called standard, therapy.

• Stem-cell transplantation is more effective than conventional chemotherapy in killing myeloma cells. However, it is a physically and emotionally demanding treatment, so not everyone with myeloma is a candidate for such an aggressive approach.Stem cell transplantation is most often used for younger patients or selected older patients with a good performance status. It has been associated with higher remission rates, as well as longer remission and survival than those of standard-dose chemotherapy.
  
  
• This procedure involves the use of very high doses of chemotherapy to kill the aggressive cancer cells.
  
  
• The chemotherapy dose is designed to destroy the marrow, in essence to keep the marrow from spontaneously recovering and producing abnormal cells once again.
  
  
• The individual is then given a transfusion of healthy bone marrow stem cells. The number of cells infused is calculated to be sufficient to induce marrow recovery with the bone marrow stemcell precursors. Conceptually, an allogenic (from a tissue-matched family donor) stem cell transplant would be preferable, in order to infuse tumor-free stem cells. However, because myeloma is a disease of the elderly, few patients may meet criteria for such an aggressive approach, and those who undergo standard allogeneic transplantation are at higher risk of complications and death.
  
  
• Should one's own stem cells be used, the reinfusion after high-dose therapy is referred to as autologous (one's own).Autologous re-infusion, or transplantation,of stem cells is a frequent treatment recommendation for patients with aggressive myelomas. It may be the only recourse if an allogeneic donor is unavailable, but it is more tolerable and associated with better survival than standard allogeneic transplantation. Nevertheless, the outcome is less likely to result in myeloma-free survival because of the uncertainty that the autologous marrow is completely disease free.
  
  
• Nonetheless, early autologous transplant, compared with continuation of chemotherapy and delayed transplant in several studies, was associated with a longer symptom-free interval.
  
  
• Allogeneic transplant may be recommended for long-term control of disease; however, such an approach is associated with higher morbidity and mortality rates compared to younger patients and those with other diagnoses. Recently, however, there have been a number of clinical trials evaluating the outcomes of patients who have received less intensive, "nonmyeloablative" transplants, sometimes referred to as "mini-transplants."A tissue-compatible family donor is still required for such a procedure, but it is associated with lower mortality rates compared with those of standard allogeneic transplant. The idea behind such an approach is to administer lower doses of chemotherapy to minimize organ damage, and to use allogeneic stem cells to exert an immune reaction against the myeloma, called "graft versus myeloma" effect.

Supportive care

Supportive care is very important in the management of all cancers, and myeloma is no exception. The following issues should be addressed in controlling the complications of the disease:

• Bone stabilization:A class of drugs, the bisphosphonates,is able to slow bone damage, reduce the risk of fractures, and reduce pain due to thinning of bone. They also regulate calcium levels in the blood and possibly affect the immune system in ways that may help fight the myeloma. These drugs are given intravenously, generally once every 3-4 weeks. Examples include pamidronate (Aredia) and zoledronic acid (Zometa).Other bisphosphonates are undergoing development or further evaluation.
  
  
• Pain control: Osteolytic lesions and the resulting fractures can cause considerable pain. Patients with myeloma often require pain-reducing medications or radiation to painful lesions.
  
  
• Orthopedic care: The fractures from osteolytic damage can cause severe pain and disability. A bone specialist (orthopedist) may provide relief from pain and improve functionality of the affected bones, if necessary. Neurosurgeons, orthopedists, or interventional radiologists may offer a procedure called vertebroplasty (injection of bone cement) to stabilize affected bones in the spine.
  
  
• Growth factors: These agents boost production of new blood cells from the bone marrow and aid in recovery from the effects of chemotherapy.